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Flashcards in Renal endocrinology Deck (69)
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1

What is the action of parathyroid hormone?

Increase blood concentrations of calcium

2

How does parathyroid hormone carry out its function?

- Stimualtes production of calcitriol in kidney
- Facilitates mobilisation of calcium and phosphate from bone
- Maximise tubular reabsorption of calcium within teh kidney

3

What is the action of calcitonin?

Decrease blood calcium

4

How does calcitonin carry out its function?

- Suppress renal tubular reabsorption of calcium
- Inhibits bone resorption

5

Why are calcium and phosphorous considered together?

- Ratio
- React in opposite ways
- As calcium increases, phosphate falls and vice versa
- Can bind together

6

How are calcium and phosphorous linked to iron?

- Are all divalent ions, so need ion transported in order to be absorbed from GI tract
- Compete for these transporters
- I.e. excess calcium in diet leads to iron deficiency

7

Describe the actions of magnesium in the body

- Enzyme cofactor
- Needed for regulation of blood glucose, production of energy and protein, nerve transmission, muscle contraction, bone and cel formation

8

What is unusual about magnesium in ruminants?

- Is absorbed from rumen
- In otehers is absorbed from small and large intestine

9

What condition is caused by low magnesium intake? What are the signs?

- Hypomagnesaemic tetany
- Aka Grass Staggers
- Often cows
- Weakness, muscle cramps, tremors

10

Why does renal failure often lead to derangements of calcium and phosphorous?

- Calcitriol synthesised in kidney
- No calcitriol = no absorption of calcium from intestine = deficiency
- Tubular reabsorption of calcium in the kidney

11

Why does bone demineralisation occur in renal failure?

- Increased PTH to increase blood calcium
- No calcitriol to feedback to stop PTH production
- PTH continues to be produced, causes bone resorption

12

What is RAAS?

Renin angiotensin aldosterone system

13

What are the mechanisms of autoregulation of renal blood flow?

- Myogenic feedback
- Tubuloglomerular feedback

14

Describe myogenic feedback in high bood pressure

- Increased renal blood flow
- Stretch vascular smooth muscle in afferent arteriole
- Calcium entry, release of more Ca from internal stores
- Automatic constriction of afferent arteriole to reduce glow to glomerulus and decrease GFR

15

Describe myogenic feedback low blood pressure

- Reduced renal blood flow
- Reduced stretch of vascular smooth muscle
- Automatic vasodilation of afferent to increase flow to glomerulus (increase GFR)

16

Why is the renal myogenic response considered to be pre-renal?

Controls the blood going into the renal corpuscle

17

Describe the mechanisms of tubuloglomerular feedback

- Signal from distal tubule to glomerulus to reciprocally alter filtration
- Decrease flow rate in ascending LoH = increase GFR in same nephron
- Also related to NaCl levels in tubular fluid

18

Describe the effect of NaCl in tubuloglomerular feedback

- NaCl low, cells at macula densa generate less adenosine
- Stimulates decreased intracellular Ca in VSMC = afferent vasodilation
- Reverse with high NaCl

19

What is the action of prostaglandins and nitric oxide on the afferent arteriole?

Vasodilate (to protect against severe vasoconstriction)

20

What occurs in acute heamorrhage?

- Intrinsic mechanisms of kidney (myogenic and tubuloglomerular feedback)
- Extrinsic mechansms e.g. sympathetic system, angiotensin II, endothelin, prostaglandins, nitric oxide
- Main aim is to maintain pressure to brain, massive total peripheral vasoconstricton

21

How does the kidney control blood pressure?

- Water balance (blood volume directly impacts blood pressure)
- Hormonal (stimulation of RAAS)
- Macula densa
- Acts to monitor blood pressure and stimulate hormonal systems, since recevies 20% of cardiac output and has high perfusion

22

What are the components of the RAAS and where are these produced what is their stimulation?

- Renin: kidney, low perfusion
- Angiotensin: liver, in response to renin
- Aldosterone: adrenal gland cortex in response to Ang II

23

Describe how the RAAS works

- Low perfusion sensed by kidney
- Release of renin
- Catalyses conversion of angiotensinogen to angiotensin I
- Angiotensin I to angiotensin II using ACE from lungs and endothelial cells
- Angiotensin II to adrenal cortex to stimulate aldosterone secretion
- Aldosterone acts on kidney to increase Na retention

24

What are the actions of angiotensin II?

- Increase sympathetic activity
- Increase Na, Cl reabsorption, K_ excretion and thus H2O retention
- Stimulate aldosterone secretion
- Arteriolar vasoconstriction to increase blood pressure
- Stimulate ADH secretion to increase collecting duct reabsorption of H2O

25

What is the action of RAAS in relation to blood pressure?

- Stabilise blood pressure rapidly
- Enables variable salt intake whilst maintaining ECF volume and thus arterial pressure

26

What is the function of the macula densa?

- Senses distal tubule and afferent/efferent arterioles
- Increase or decrease nerve firing and flow rate in response

27

Describe the overall effect of RAAS

- Loss of blood volume > redcued ECF > BP falls > renal flow falls > tubular flow decreased > less NaCl to macula densa > stimualtes renin from juxtaglomerular apparatus > increased intrarenal and systemic Ang II > increase systemic and intrarenal resistance > support continued filtration despite reduced RBF adn increased peripheral vascular resistance

28

How does angiotensin II exert its actions in the renal tubules as a whole?

Insertion of Na+ channels in renal tubules via AT1 receptors
-

29

How does angiotensin II exert its actions in the proximal tubule?

- Inserts apical Na+/H+ exchanger
- Inserts basolater Na+3(HCO3-) and Na+/K+ ATPase

30

How does angiotensin II exert its actions in the thick ascending limb?

- Inserts apical Na+/H+ exchanger
- Na+K+2Cl- pump

31

How does angiotensin II exert its actions in the collecting duct?

Inserts epithelial Na+ channel (ENaC)

32

What is the function of ACE?

- Angiotensin converting enzyme
- Converts angiotensin I to angiotensin II

33

What are the actions of AngII in cardiac disease?

- Contraction of vascular smooth muscle produces vasoconstriction
- Stimulates aldosterone secretion from adrenal cortex
- Increases sodium reabsorption in proximal tubule
- Stimulates hypertrophy of myocardiac and vascular smooth muscle
- Stimulates thirst receptors in brain
- Enhanced adrenergic tone and increased release of noradrenaline from sympathetic nerve terminals
- increases endothelin release, may cause vasoconstriction
- Increased BP, furhtering heart disease

34

What is the role of AngII in renal disease?

- Increased glomerular capillary pressure (efferent vasoconstriction)
- Increased glomerular protein loss
- Activaton of inflam cells
- Development of systemic hypertension associated with some renal disease, can contribute to progressive renal damage

35

What is the function of ACE inhibitors?

- Inhibit ACE
- Thus reduce activity of AngII

36

What are the systemic actions of ACE inhibitors

- Inhibits Ang-II production
- Lack of vasoconstriction
- Reduced aldosterone production
- Inhibit hypertrophy of myocardium and smooth muscle
- Decrease water intake
- Decrease sympathetic activation
- Decrease vasopressin release

37

Why are ACE inhibitors considered balanced vasodilators?

Dilate arteries and veins equally

38

What is the significance of ACE inhibitors?

Are the only vasodilators to counteract RAAS

39

What are the ocal actions of ACE inhibitors?

- Local RAAS exist in various tissues (cardiac, vascular, renal) and can be inhibited
- Inhibit hypertrophy and fibrosis (chornic activation by Ang-II) in heart and blood vessels
- Reduce glomerular capillary hypertension in kidney

40

What is the importance of reducing glomerular capillary hypertension using ACE inhibitors?

- Reduces proteinuria
- Reduce nephron loss and thus replacemet with collagen
- Would lead to glomerulosclerosis and intersitial fibrosis, thus loss of renal function

41

Describe the beneficial actions of ACE inhibitors in congestive heart failure

- Balanced vasodilation (decrease in systemic, pulmonary and atrial pressures decreasing venous ceongestion and excessive load on myocardium)
- Decreased sodium and water retention reducing circulating fluid and decreasing venous congestion
- Decreasing myocardial (and vascular) hypertrophy and fibrosis

42

Describe the beneficial actions of ACE inhibitors in renal failure

- Decreased efferent renal arteriolar resistance, increase coefficient of glomerular ultrafiltration
- Reduction in glomerular hypertension
- Decreased magnitude of proteinuria (hyperproteinuric renal disease)
- Decreased blood pressure (hypertensive renal diseae)

43

Give examples of ACE inhibitors

Enalapril, benazapril, ramipril, imidapril

44

What are the risks of using ACE inhibitors?

- Teratogenic
- May tip some dogs/cats with pre-existing renal disease and proteinuria into acute renal crisis due to effects on tubular perfusion

45

List the factors influencing RAAS

- Hypertension
- ACE inhibitors
- Angiotensin receptor blockers
- Beta-blockers (inhibit renin)
- Low sodium diets
- Diuretics
- Ca2+ channel antagonists
- Alpha-1 blockers
- SNS activity

46

Explain the nephrotoxic action of NSAIDs

- Inhibit afferent arteriole vasodilators
- Less blood to nephron
- NO perfusion
- No glomerular filtrate
- Injury cannot be repaired

47

Give examples of alternatives to ACEi

- ANG-II receptor blockers
- Ca channel blockers

48

What is the role of the kidney in the production of new red blood cells?

- Kidneys produce EPO
- EPO stimulates proliferation and terminal differentiation of red blood cells

49

Where in the kidneyis EPO produced?

- Interstitial fibroblasts
- In association with peritubular capillary and proximal convoluted tubule

50

Which region of the kidney is particulary vulnerable to ischaemic damage?

Renal medulla

51

Why is the kidney particularly vulnerable to ischaemic damage?

- High oxygen consumption in outer medulla
- Major recipient of cardiac output
- High metabolic activity (high impact by hypertension)
- Multiple complex enzyme pathways

52

Why might EPO be beneficial as a drug for renal failure?

- Prevents anaemia
- Prevents reception of low perfusion
- Hypertension will not increase, limits damage

53

Why are older cats susceptible to renal disease?

- Toxins, infections, hypertension, high protein diet
- Physiological cahnges when aging
- Vulnerable to ibuprofen and antifreeze

54

Describe calcium uptake in the proximal tubules and thick ascending limb of LoH

- Passive, driven largely by Na uptake
- Ca leak channels, paracellular as tubular Ca increases down tubules due to isosmotic water uptake

55

Describe calcium uptake in the distal tubule

- Active, transcellular
- Epithelial apical ca channels
- Intracellular transport by Ca-binding proteins
- Basolateral Ca-ATPase (PMCA) pumps Ca back to body
- Basolateral 3Na/Ca antiporter (NCX) pumps Ca back to body

56

Explain the action of PTH and vit D in increasing Calcium reabsorption in the distal tubule

- Epithelial apical channels activated by PTH
- Intracellular transport proteins upregulated by vit-D
- Basolateral Ca-ATPase stimulated by vit-D and PTH

57

How can secondary hyperparathyroidism occur?

- In response to hypocalcaemia
- e.g. excess plasma P binding to Ca, perceive low Ca = release of PTH
- Also excess exercise/sweating in horses

58

How can secondary hypoparathyroidism occur?

- Renal disease, Ca and P excreted less
- Increase plasma Ca and P therefore increase in PTH

59

Describe phosphate in the kidney

- Non-protein bound freely filtered
- 80% reabsorbed in proximal tubule, transcellular with Na (NPT2)
- No significant uptake in loop
- DT and CD similar to PT

60

What is the effect of PTH on phosphate reabsorption?

Inhibits reabsorption

61

How does hyperphosphataemia occur?

- Increased dietary intake
- Decreased renal excretion (e.g. urinary tract obstruction, rupture, renal failure)
- Cell lysis releasing P
- Hyperthyroidism

62

How does hyperphosphataemia occur in chronic kidney disease?

- Increase in blood PTH from CKD
- Stimualtes increased renal excretion of Pa, decreased Ca excretion
- Inadequate in late CKD, hyperphosphataemia
- PTH high, bone resorption, more P present
- Inhibition of calcitriol production so reduced Ca absorption

63

What may reduce P excretion in acute kidney disease?

Decreased GFR

64

Describe the renal handling of Mg

- Non-protein bound freely filtered
- 30% reabsorbed in PT (passive, trans-epithelial gradietn)
- 65% in TAL
- 5% in DT (active uptake)

65

Describe the reabsorption of MG in the distal tubule

- Active
- Apical Mg channel (TRPM6)
- Open state of channel influenced by intracellular [Mg]
- Basolateral Mg-ATPase

66

What is the effect of PTH and calcitonin on Mg reabsorption?

Increase passive reabsorption

67

Describe the mechanisms behind changes in body calcium and phosphorous levels in renal failure

- Renal failure = reduced excretion of P and decreased reabsorption of Ca
- P and Ca bind, lead to hypocalcaemia and hyperphosphataemia

68

Explain how secondary hyperparathyroidism occurs

- Renal failure, decreased P excretion, increase in serum P
- Increased serum P binds to Ca
- Decrease in free Ca
- PTH secretion
- Decreased calcitriol formation due to renal failure, decreased Ca uptake from gut, further increase in PTH (no negative feedback)

69

What can be done to treat secondary hyperparathyroidism?

- Dietary phosphate restriction
- Phosphate binders
- Calcitriol therapy
- Treat underlying cause